Cabometyx’s Cabinet committee
Exelixis hopes to become a leader in neuroendocrine tumours with its kinase inhibitor Cabometyx, but the FDA might have other ideas. The agency has convened an advisory committee meeting to discuss the supporting Cabinet trial, which hit its primary endpoint of progression-free survival, but didn’t show Cabometyx conferring an overall survival benefit versus placebo. The NCI-sponsored study in relapsed NETs, presented at ESMO this year, could have been confounded by a high rate of crossover and treatment with subsequent therapies. The data and safety monitoring board, which unblinded the study in August 2023 after finding a PFS benefit, no doubt believed that it was unethical to let patients continue on placebo; however, there could also be questions about why an active control wasn’t used. Addressing this, the investigators noted in the NEJM that the efficacy of therapy after progression on Novartis’s Lutathera and/or targeted agents “has not been well established”, adding that patients could have received all available therapies before enrolling in Cabinet. Cabometyx isn’t without risk: four patients in the extrapancreatic NET cohort suffered possibly drug-related fatal events. These could all be talking points at the March 2025 adcom; Cabometyx has a 3 April PDUFA date.
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